Adenosine deaminase (ADA), an important enzyme of the purine salvage pathway, converts adenosine, deoxyadenosine and water into inosine and ammonia. Individuals who harbor deleterious mutations in the ADA gene can develop varying degrees of immunodeficiency disorder, from mild to severe Such immunodeficiency disorder is due to the toxic accumulation of the enzyme substrates, adenosine and deoxyadenosine, in the immature lymphoid cells. The onset of the disorder can also range from early childhood to adults, depending on the mutations inherited. Deficiencies of ADA are one of the leading causes of severe combined immunodeficiency disease (SCID) in children and is one of the leading targets for gene therapy approaches (R. Parkman et al., 2000, “Gene therapy for adenosine deaminase deficiency”, Ann. Rev. Med., 51:33–47).
The present invention relates to the isolation, characterization and use of a novel polynucleotide encoding a human adenosine deaminase homolog.